Various methods are available for the transfer of genetic information and proteins to cells. However, there remains a need in the art to provide localized, high efficiency transfer of genetic information and proteins to cells and tissues, such that long-term benefits are provided. In particular, methods and compositions are needed for settings such as wound healing.
For example, during the process of healing, infection can occur. Indeed, infections represent a significant health risk to various patients, including hospitalised individuals, as well as those with underlying disease conditions and/or immune defects. In particular, wounds and infections represent a serious risk to diabetic patients. These patients often experience slow and/or incomplete wound healing, ulceration of the extremities, and are prone to infection. In diabetic patients, ulcers are often large, open wounds that can involve both soft tissue and the underlying bone. The problem is widespread, as approximately 15% of all diabetics develop ulcers. Infections within these ulcers are difficult to successfully treat, due to poor circulation at these sites (e.g., limiting the potential for systemically administered antimicrobial treatments to reach the wound sites). In extreme cases, limb amputation becomes necessary. Indeed, these amputations account for half of all amputations done in the U.S. Thus, wounds and ulcers of diabetic patients often represent life threatening conditions for diabetic subjects.
Current treatment of diabetic wounds or ulcers consists of debridement, packing the wound with gauze, and placing the patient on systemic antimicrobials. However, no evidence exists that an adequate amount of drug reaches the wound site with this treatment. Indeed, there remains a need for compositions and methods for improved wound healing for administration to diabetic individuals.
Wound repair is a complex process involving the continual communication and interaction between fibroblasts, endothelial cells, keratinocytes, inflammatory cells and the extracellular matrix (ECM). Efficient wound repair requires adequate formation of granulation tissue to maintain a supply of nutrients in the wound area (Arbiser, J. Am. Acad. Dermatol., 34:486-497 [1996]; and Gallit and Clark, Curr. Op. Cell. Biol., 6:717-725 [1994]), and for extracellular matrix deposition (collagen synthesis). When collagen synthesis is impaired or inhibited, wounds heal slowly and incompletely (Streit et al., EMBO 19:3272-3282 [2000]; and Goodson and Hunt, J. Surg. Res., 22:221-227 [1997]). Thus, what is needed are means to facilitate wound healing, particularly in individuals with impaired and/or incomplete wound healing capabilities, such as diabetic individuals.